ABBOTT PRISM HIV O Plus 3L68-68 G10316R06 Read Highlighted Changes: Human Immunodeficiency Virus Revised March 2019 Types 1 and 2 (E

en ABBOTT PRISM HIV O Plus 3L68-68 G10316R06 Read Highlighted Changes: Human Immunodeficiency Virus Revised March 2019 Types 1 and 2 (E. coli, B. megaterium, Recombinant) Antigen and Synthetic Peptide

Customer Service: Contact your local representative or find country specific contact information on www.abbottdiagnostics.com Package insert instructions must be carefully followed. Reliability of assay results cannot be guaranteed if there are any deviations from the instructions in this package insert.

Key to Symbols

Caution Conjugate Wash PROBE 20X CONC Probe 20X Concentrate

Contains Sodium Azide. Consult instructions Contact with acids liberates PROBE DILUENT Probe Diuent for use very toxic gas.

Manufacturer Danger: Reproductive Hazard Probe Wash

Store at 2-8°C Distributed by Produced for Abbott by

Authorized Representative in Store at 15-30°C Product of USA the European Community

Use by/Expiration HIV-1 CONTROL + HIV-1 Positive Control Purge Concentrate date

Activator HIV-2 CONTROL + HIV-2 Positive Control Reaction Trays Concentrate

In Vitro Diagnostic Medical Activator Diluent Reagent Components Device

Activator Line Line Cleaner List Number Treatment

Assay Kit Card Lot Number Run Control Adapters

Negative Calibrator Master Lot Sample Cups

Positive Calibrator Microparticles Transfer Wash

Warning: May cause an Calibrators Pipette Tips allergic reaction

Conjugate Prime/Purge Accessories Warning: Severe Irritant

See REAGENTS section for a full explanation of symbols used in reagent component naming. U.S. License No. 43

1 NAME AND INTENDED USE The amount of light emitted is proportional to the amount of anti-HIV-1 The ABBOTT PRISM HIV O Plus assay is an in vitro chemiluminescent and/or anti-HIV-2 in the sample. The presence or absence of immunoassay (ChLIA) for the qualitative detection of antibodies to HIV-1 anti-HIV-1/HIV-2 in the sample is determined by comparing the number (anti-HIV-1) Groups M and O and/or antibodies to HIV-2 (anti-HIV-2) in of photons collected from the sample to a cutoff value determined from human serum and plasma specimens. The ABBOTT PRISM HIV O Plus a calibration performed in the same batch. If the number of photons assay is intended to screen individual human donors, including volunteer collected from a test sample is less than the cutoff value, the sample donors of Whole Blood and blood components and other living donors, for is considered nonreactive for anti-HIV-1 and anti-HIV-2 by the criteria of the presence of anti-HIV-1 Groups M and O and/or anti-HIV-2. The assay the ABBOTT PRISM HIV O Plus assay. These specimens need not be is also intended for use in testing blood and plasma specimens to screen further tested. If the number of photons collected from a test sample is organ donors when specimens are obtained while the donor’s heart is still greater than or equal to the cutoff value, the sample is considered reactive beating, in testing blood specimens to screen cadaveric (non–heart-beating) for anti-HIV-1 and/or anti-HIV-2 by the criteria of the ABBOTT PRISM donors, and as an aid in the diagnosis of HIV-1/HIV-2 infection. It is not HIV O Plus assay. Specimens that are initially reactive must be handled as intended for use in testing cord blood specimens. described in the Preparation for Analysis section of this package insert and retested in duplicate. Reactivity in either or both of these duplicate SUMMARY AND EXPLANATION OF THE TEST tests (i.e., repeatedly reactive) is highly predictive of the presence of The ABBOTT PRISM HIV O Plus assay uses recombinant DNA-derived HIV-1 and/or HIV-2 antibodies in individuals at risk for HIV infection. Follow antigens corresponding to three viral proteins (HIV-1 Group M envelope, appropriate FDA recommendations and regulations for specimens found to HIV-1 Group O envelope, and HIV-2 envelope) and one synthetic peptide be repeatedly reactive. Customers outside the US must follow their country’s corresponding to HIV-2 envelope. government recommendations and regulations for specimens found to be Epidemiologic data suggest that the acquired immunodeficiency syndrome repeatedly reactive. For further information regarding ChLIA technology, (AIDS) is caused by at least two types of human immunodeficiency viruses, refer to the ABBOTT PRISM Operations Manual, Section 3. collectively designated HIV. Human immunodeficiency virus type 1 (HIV-1), Repeatedly reactive specimens obtained from people at risk for HIV the first-discovered AIDS virus, has been isolated from patients with AIDS infection are usually found to contain antibodies by supplemental tests and from healthy persons at high risk for AIDS.1-3 HIV-1 is transmitted by included in the FDA or other country’s recommendations. Certain sexual contact, by exposure to blood or blood products, or by an infected specimens may require nucleic acid amplification testing or culture to mother to her fetus or child.4 ensure confirmation. A full differential diagnostic workup for the diagnosis HIV-2 was isolated from patients with AIDS in West Africa.5 The HIV-2 virus of AIDS and AIDS-related conditions necessarily includes an examination is similar to the HIV-1 virus in its morphology, cell tropism, interaction with of the patient’s immune status and clinical history. the CD4 cellular receptor, in vitro cytopathic effect on CD4 cells, overall genomic structure, transmission route, and its ability to cause AIDS.5-8 REAGENTS NOTE: Each specific component description that follows is accompanied HIV-2 has not spread substantially outside of West Africa; the prevalence by a unique symbol. These symbols appear on both the component labels of HIV-2 in North and South America and Europe is low. HIV-2 prevalence and on corresponding instrument tubing identifier labels. They are meant to is stable or declining in West African countries.8 facilitate identification and installation of reagent bottles within the ABBOTT HIV-1 isolates have been classified into three groups: Group M (main), PRISM System ambient reagent bay and refrigerator. Group O (outlier), and Group N (non-M/non-O). Group M has 9 subtypes (A, ABBOTT PRISM HIV O Plus Assay Kit ( 3L68-68) B, C, D, F, G, H, J, K) and many circulating recombinant forms (CRFs).9,10 Group M has been identified worldwide; however, the geographic distribution NOTE: Do not mix reagents from different bottles. Do not mix or interchange and regional predominance of Group M subtypes vary with epidemiological reagents from different ABBOTT PRISM HIV O Plus Assay Kits. spread. All HIV-1 Group M subtypes have been found in Africa.11-13 • 1 Bottle (324 mL) HIV-1/HIV-2 (E. coli, B. megaterium, The predominant strain in North America, South America, Europe, and recombinant) antigen coated microparticles in phosphate buffer Australia is subtype B, although other subtypes are also present in these with CHAPS. Minimum activity with PC: 3.00 S/CO, Minimum activity regions.11-13 The predominant strains in Southeast Asia are CRF01_AE with PC2: 2.00 S/CO, Minimum activity with OPC: 1.50 S/CO. (formerly subtype E) and subtype B, while the predominant strains in India Preservative: 0.1% sodium azide. (Symbol:  ) are subtype C.11-13 Group O is found primarily in Cameroon and west • 1 Bottle (331 mL) Anti-biotin (mouse monoclonal): central Africa, but also has been identified in the US and Europe.14-19 acridinium conjugate in phosphate buffered saline with Triton X-100 and HIV-1 Group O was identified as a strain highly divergent from the Group protein stabilizers. Minimum concentration: 0.050 µg/mL. Preservative: M strains.20,21 The genetic diversity within Group O strains is similar to the 0.1% sodium azide. (Symbol: ) level of diversity among Group M strains; however, Group O strains have • 3 Bottles (10.4 mL each) Negative Calibrator. Recalcified human not been classified into subtypes.22 Group N has been identified only in plasma. Preservative: 0.1% sodium azide. (Symbol: NC) 23-25 Cameroon and is rare. The global distribution and predominance of • 3 Bottles (10.4 mL each) Positive Calibrator. Recalcified, HIV-1 strains are affected by epidemiological factors and will continue to inactivated, human plasma reactive for anti-HIV-1. Minimum activity: 11-13 change over time. 3.00 S/CO. Preservative: 0.1% sodium azide. (Symbol: PC) BIOLOGICAL PRINCIPLES OF THE PROCEDURE • HIV-2 CONTROL + 3 Bottles (10.4 mL each) HIV-2 Positive Assay The ABBOTT PRISM HIV O Plus assay is a three-step sandwich ChLIA. The Control (1). Recalcified, inactivated, human plasma reactive for reactions occur within the ABBOTT PRISM System in the following sequence: anti-HIV-2. Minimum activity: 2.00 S/CO. Preservative: 0.1% sodium azide. (Symbol PC2) • Microparticles coated with HIV antigens (recombinant proteins) are incubated with sample (either plasma, serum, calibrator, or control) NOTE: The ABBOTT PRISM HIV O Plus Calibration Report identifies in the incubation well of the reaction tray. During incubation, HIV-1 and/ the ABBOTT PRISM HIV O Plus HIV-2 Positive Assay Control (PC2) or HIV-2 antibodies present in the sample bind to the antigen(s) on as “Pos Assay CTL (1).” the microparticles. • HIV-1 CONTROL + 3 Bottles (10.4 mL each) HIV-1 Group O Positive • After this first incubation is complete, the reaction mixture is transferred Assay Control (2) containing HIV-1 Group O (mouse monoclonal) to the glass fiber matrix (matrix) of the reaction tray using the transfer antibody in recalcified human plasma. Minimum activity: 1.50 S/CO. wash. The microparticles are captured by the matrix, while the Preservative: 0.1% sodium azide. (Symbol: OPC) remaining mixture flows through to an absorbent blotter. NOTE: The ABBOTT PRISM HIV O Plus Calibration Report identifies • A probe mixture (probe) consisting of biotinylated HIV-1 recombinant the ABBOTT PRISM HIV O Plus HIV-1 Group O Positive Assay Control proteins and biotinylated HIV-2 peptide is added to the microparticles (OPC) as “Pos Assay CTL (2).” on the matrix and incubated. The probe binds to the microparticle- • PROBE 20X CONC 1 Bottle (16 mL) Probe 20x Concentrate containing antibody complex created during the first incubation process. After biotinylated HIV-1/HIV-2 (E. coli, recombinant) antigen and synthetic the second incubation, the unbound probe is washed into the blotter peptide in borate buffer with protein stabilizers. Minimum concentration: with the probe wash. 6.54 µg/mL. Preservative: 0.1% sodium azide. (No Symbol) • The acridinium-labeled anti-biotin conjugate is added to the NOTE: Probe 20x Concentrate MUST be mixed with Probe Diluent microparticles on the matrix and incubated to bind any probe that is prior to use. present. After the third incubation, the unbound conjugate is washed • PROBE DILUENT 1 Bottle (306 mL) Probe Diluent. Borate buffer with into the blotter with the conjugate wash. protein lysate and protein stabilizers. Preservative: 0.1% sodium azide. • The chemiluminescent signal is generated by addition of an alkaline (Symbol: ) hydrogen peroxide solution. The resultant photons are counted. NOTE: Probe Diluent MUST be mixed with Probe 20x Concentrate prior to use.

2 Other Reagents Required WARNING: Contains sodium azide and polyethylene glycol ABBOTT PRISM HIV O Plus Wash Kit ( 3L68-58) octylphenyl ether. • 1 Bottle (3364 mL) Transfer Wash. Borate buffered EUH032 Contact with acids liberates very toxic gas. saline. Preservative: 0.1% sodium azide. (Symbol: ) H401 Toxic to aquatic life. • 1 Bottle (2794 mL) Conjugate Wash. TRIS buffer. H411 Toxic to aquatic life with long lasting effects. Preservative: 0.1% sodium azide. (Symbol: ) Prevention • PROBE WASH 1 Bottle (2258 mL) Probe Wash. TRIS buffer. Preservative: P273 Avoid release to the environment. 0.1% sodium azide. (Symbol: ) Disposal ABBOTT PRISM Activator Concentrate ( 1A75-02 or 3L27-02) P501 Dispose of contents / container in accordance with local regulations. • 4 Bottles (900 mL each) Activator Concentrate. 0.4% hydrogen peroxide/0.06% diethylenetriaminepentaacetic acid. • The following warnings and precautions apply to the ABBOTT PRISM Activator Diluent ( 1A75-01 or 3L27-01) WARNING: Contains methylisothiazolones. • 4 Bottles (900 mL each) Activator Diluent. 0.3 N H 317 May cause an allergic skin reaction. sodium hydroxide. Prevention ABBOTT PRISM Run Control Kit ( 3E60-10) P261 Avoid breathing mist / vapours / spray. Or P272 Contaminated work clothing should not be ABBOTT PRISM Positive Run Control Kit ( 3E60-11) allowed out of the workplace. NOTE: Each batch MUST end in a release control (ABBOTT PRISM P280 Wear protective gloves / protective clothing / Positive Control). The ABBOTT PRISM Positive Control (included in Kit eye protection. 3E60-10 or 3E60-11) must be used as the release control, which has Response been configured to validate the system functionality and release sample P302+P352 IF ON SKIN: Wash with plenty of water. results. Refer to the ABBOTT PRISM Run Control Kit package insert or P333+P313 If skin irritation or rash occurs: Get medical the ABBOTT PRISM Positive Run Control Kit package insert for detailed advice / attention. handling and use instructions. P362+P364 Take off contaminated clothing and wash it before reuse. WARNINGS AND PRECAUTIONS Disposal • P501 Dispose of contents/container in accordance • For In Vitro Diagnostic Use with local regulations. • Package insert instructions must be carefully followed. Reliability of • The following warnings and precautions apply to these components: assay results cannot be guaranteed if there are any deviations from PROBE 20X CONC the instructions in this package insert. • • PROBE DILUENT Safety Precautions DANGER: Contains boric acid, disodium tetraborate decahydrate and sodium azide. • CAUTION: This product contains human-sourced and/or potentially H360 May damage fertility or the unborn child. infectious components. Refer to the REAGENTS section of this package EUH032 Contact with acids liberates very toxic gas. insert. No known test method can offer complete assurance that Prevention products derived from human sources or inactivated microorganisms P201 Obtain special instructions before use. will not transmit infection. Therefore, all human-sourced materials should be considered potentially infectious. It is recommended that P280 Wear protective gloves / protective clothing / these reagents and human specimens be handled in accordance with eye protection. the OSHA Standard on Bloodborne Pathogens26. Biosafety Level 227 or Response other appropriate biosafety practices28,29 should be used for materials P308+P313 IF exposed or concerned: Get medical that contain or are suspected of containing infectious agents. These advice / attention. precautions include, but are not limited to, the following: Disposal 1. Wear gloves when handling specimens or reagents. P501 Dispose of contents/container in accordance with local regulations. 2. Do not pipette by mouth. 3. Do not eat, drink, smoke, apply cosmetics, or handle contact lenses • This product contains sodium azide; for a specific listing, refer to the in areas where specimens or reagents are handled. REAGENTS section of this package insert. Contact with acids liberates very toxic gas. This material and its container must be disposed of 4. Clean and disinfect all spills of specimens or reagents using in a safe way. an appropriate disinfectant such as 0.1% sodium hypochlorite, or other suitable disinfectant.30,31 • Safety Data Sheets are available at www.abbottdiagnostics.com or contact your local representative. 5. Decontaminate and dispose of all specimens, reagents, and other potentially contaminated materials in accordance with local, state, and Handling Precautions federal regulations.32,33 • Do not use kits beyond the expiration date. • The human plasma used in the negative calibrator is nonreactive for • Gently invert each component several times prior to loading the original HBsAg, HIV-1 RNA or HIV-1 Ag, anti-HIV-1/HIV-2, and anti-HCV. container on the ABBOTT PRISM System to ensure a homogeneous • The human plasma used in the positive calibrator is reactive for solution. Additional gentle inversion may be required to thoroughly anti-HIV-1. Plasma is also tested for HIV-1 either by an HIV-1 antigen resuspend microparticles. Avoid foaming. test and is nonreactive, or by an HIV-1 NAT, and may be reactive. • Gently invert calibrators and assay controls in the calibrator pack several Plasma is nonreactive for HBsAg and anti-HCV. times prior to each use. • The human plasma used in the HIV-2 Positive Assay Control (1) is • Each component of the ABBOTT PRISM HIV O Plus Wash Kit should reactive for anti-HIV-2 and nonreactive for HBsAg, HIV-1 RNA or HIV-1 Ag, be at room temperature (15-30°C) and then mixed before loading onto and anti-HCV. the ABBOTT PRISM System. • The human plasma used in the HIV-1 Group O Positive Assay Control (2) • Do not mix reagents or calibrators/assay controls from different bottles. contains HIV-1 Group O (mouse monoclonal) antibody in recalcified Do not mix or interchange reagents from different ABBOTT PRISM HIV human plasma. Plasma is nonreactive for HBsAg, HIV-1 RNA or HIV-1 Ag, O Plus Assay Kits. anti-HIV-1/HIV-2, and anti-HCV. • Any lot of ABBOTT PRISM HIV O Plus Wash Kit can be used with any The following warnings and precautions apply to , lot of ABBOTT PRISM HIV O Plus Assay Kit. , , HIV-1 CONTROL + , HIV-2 CONTROL + : • Any lot of ABBOTT PRISM Activator Concentrate, ABBOTT PRISM Contains sodium azide. Activator Diluent, and Control from an ABBOTT PRISM Run Control EUH032 Contact with acids liberates very toxic gas. Kit or ABBOTT PRISM Positive Run Control Kit may be used with any lot of ABBOTT PRISM Assay Kit. P501 Dispose of contents / container in accordance with local regulations. • Treat negative and positive calibrators and controls as potentially infectious. • The following warnings and precautions apply to • Avoid microbial and chemical contamination of samples, reagents, and

3 equipment. The use of disposable pipette tips is recommended for any INSTRUMENT PROCEDURE preliminary sample transfer. • For the software versions that may be used to perform the assay, • Use accurately calibrated equipment. refer to the ABBOTT PRISM Assay / Software Version Matrix • Do not freeze reagents. located in the Supplemental Information tab of the ABBOTT PRISM Operations Manual. • Failure to adhere to instructions in the ABBOTT PRISM Operations Manual or this package insert may result in erroneous test results. • Refer to the ABBOTT PRISM Operations Manual for a detailed description of instrument procedures. • Use caution when handling samples, reagent bottles, and reagent caps to prevent cross contamination. • Refer to the ABBOTT PRISM Operations Manual, Section 7, for limitations associated with test management. Additional safety and handling precautions and limitations for the assay kit, calibrators, specimens, controls, and other reagents are described in the • Solutions required for instrument cleaning and maintenance are ABBOTT PRISM Operations Manual, Sections 7 and 8. described in detail in the ABBOTT PRISM Operations Manual, Sections 5 and 9. Preparation of the Diluted Probe • For optimal performance, it is important to follow the routine NOTE: Preparation of probe solution does not require the diluent or maintenance procedures defined in the ABBOTT PRISM Operations concentrate to equilibrate to room temperature prior to combining and Manual, Section 9. mixing. 1. Carefully empty the entire contents of the small probe 20x concentrate SPECIMEN COLLECTION AND PREPARATION FOR dropper bottle into the larger probe diluent bottle by slowly squeezing ANALYSIS the dropper bottle several times while keeping the dropper tip within Specimen Types the opening of the probe diluent bottle. Avoid foaming. Solution will • For living donors, serum (including serum collected in serum separator turn light red in color. tubes), plasma collected in EDTA, potassium oxalate, sodium citrate, 2. Write the date of preparation, the date of expiration, the lot number of ACD-A, ACD-B, CP2D, CPD, or CPDA-1 anticoagulants, or plasma probe 20x concentrate ( 3L68H), and the preparer’s name on the collected from segmented tubing may be used with the ABBOTT PRISM probe diluent label on the large bottle, in the spaces provided. HIV O Plus assay. Follow the manufacturer’s specimen collection instructions for serum and plasma collection tubes. NOTE: The diluted probe must be used within 56 days of preparation. CAUTION: Do not use specimens collected in heparin. Use of heparin 3. Reseal the large bottle and mix thoroughly by slowly inverting several as an anticoagulant may cause a reduction in sample net counts and times. Do not vortex. in sample net counts/cutoff value (S/CO) for ABBOTT PRISM HCV; 4. Place in the ABBOTT PRISM System refrigerator. Refer to the therefore, heparin is not recommended for any ABBOTT PRISM assay. ABBOTT PRISM Operations Manual, Section 5, PREPARE AND LOAD • For cadaveric donors, only serum may be used; follow general standards REAGENTS, for additional information. and/or regulations for collection. Preparation of Activator Solution • Do not use cadaveric plasma specimens. Activator solution must be prepared by mixing equal parts of ABBOTT PRISM Specimen Conditions Activator Concentrate and ABBOTT PRISM Activator Diluent. The activator • This assay was designed and validated for use with individual human solution expires 24 hours from preparation. The ABBOTT PRISM Activator serum and plasma specimens. This assay has not been validated for Concentrate may be used immediately after removing from the refrigerator. use with pooled specimens. The volume of activator solution required for multiple tests is calculated • For living donors and cadaveric (non-heart-beating) donors, serum by the ABBOTT PRISM System software. Refer to the ABBOTT PRISM from heparinized patients may be incompletely coagulated resulting in Operations Manual, Section 5, PLAN WORK LOAD, for additional information. potential instrument errors such as drain time errors due to the presence Use clean pipettes and/or metal-free containers (such as plasticware or of fibrin. To prevent this phenomenon, draw specimen prior to heparin acid-washed and purified or equivalent water-rinsed glassware) to measure. therapy or after heparin therapy is discontinued and activated partial Refer to the ABBOTT PRISM Operations Manual Glossary for the definition thromboplastin time (aPTT) levels return within normal range. of purified water. Prepare the activator solution in the bottle provided in the ABBOTT PRISM Accessory Kit ( 6A36-60). Cover the bottle opening • Do not use heat-inactivated specimens. securely with the cap provided and invert gently five to ten times to mix. • Do not use specimens with obvious microbial contamination. Load the activator solution on the ABBOTT PRISM System. Refer to the • Performance has not been established using umbilical cord blood or ABBOTT PRISM Operations Manual, Section 5, PREPARE AND LOAD body fluids such as urine, saliva, semen, amniotic fluid, cerebrospinal ACTIVATOR SOLUTION, for additional information. fluid, or pleural fluid. These specimens should not be tested using the NOTE: The activator solution must be used within 24 hours of preparation. ABBOTT PRISM HIV O Plus assay. • Clear, nonhemolyzed specimens should be used when possible. Storage Instructions Specimens containing visible particulate matter may give erroneous • Store the ABBOTT PRISM HIV O Plus Assay Kit, or inconsistent test results. ABBOTT PRISM Run Control Kit, ABBOTT PRISM • No qualitative performance differences were observed when a minimum Positive Run Control Kit, and ABBOTT PRISM of 24 nonreactive and 72 low-level reactive specimens were spiked with Activator Concentrate at 2-8°C. elevated levels of bilirubin (≤ 20 mg/dL), hemoglobin (≤ 500 mg/dL), red blood cells (≤ 0.4% v/v), triglycerides (≤ 3000 mg/dL), or protein • The diluted probe must be stored at 2-8°C and used (≤ 12 g/dL). However, specimens that contain greater concentrations within 56 days of preparation. of these potentially interfering substances have not been tested. • Store the ABBOTT PRISM HIV O Plus Wash Kit The impact of greater concentrations of these potentially interfering and ABBOTT PRISM Activator Diluent at room substances on the ABBOTT PRISM HIV O Plus assay is unknown. temperature (15-30°C). Preparation for Analysis • The activator solution must be stored at 15-30°C and FAILURE TO FOLLOW THE SPECIFIED CENTRIFUGATION PROCEDURE used within 24 hours of preparation. MAY GIVE ERRONEOUS OR INCONSISTENT TEST RESULTS. • When stored and handled as directed, reagent and wash kit components are stable until the expiration date. For ABBOTT PRISM HIV O Plus, inadequate centrifugation of nonfrozen plasma specimens can lead to elevated reactive rates due to platelet • Store ABBOTT PRISM Pipette Tips and ABBOTT PRISM Reaction interference. Trays in their original packaging until use. Nonfrozen plasmapheresis specimens do not require centrifugation. All Indications of Instability or Deterioration of Reagents other specimens (including previously frozen plasmapheresis specimens) The ABBOTT PRISM System will not continue to process samples when must be centrifuged as described in this section. calibrator or positive assay control values do not meet specifications. This may indicate either deterioration or contamination of reagents, or instrument Nonfrozen SERUM specimens must be centrifuged such that g-minutes are failure. Refer to the ABBOTT PRISM Operations Manual, Section 10, for between 30,000 and 75,000. A refrigerated or nonrefrigerated centrifuge additional information. is acceptable for use. The acceptable time and force ranges that meet this criterion are listed in Table I. Any specimen that is not tested or retested within 24 hours of initial centrifugation must be recentrifuged as described in Table I. 4 NOTE: Filtered cadaveric specimens that are not tested within 24 hours of Filtration of Centrifuged Cadaveric SERUM Specimens initial centrifugation must be recentrifuged, but do not need to be refiltered. Failure to adhere to the following instructions may result in erroneous Table I: Nonfrozen SERUM Specimens or inconsistent test results. Centrifugation Time Wear personal protective equipment, including eyewear. (minutes) RCF (x g) g-minutes After centrifugation, filter each cadaveric specimen through a Millipore GV Filter as follows: 10 3,000 30,000 1. Label an empty tube with the specimen identification number matching 15 2,000 - 3,000 30,000 - 45,000 the original tube. 20 1,500 - 3,000 30,000 - 60,000 2. Remove the plunger from a sterile 10 cc syringe. 25 1,300 - 3,000 32,500 - 75,000 NOTE: Do not use a syringe smaller than 10 cc because excess pressure may build up, potentially causing damage to the filter unit or personal injury. Nonfrozen PLASMA specimens must be centrifuged such that g-minutes 3. Remove the sterile filter from the package. are between 45,000 and 75,000. A refrigerated or nonrefrigerated centrifuge is acceptable for use. The acceptable time and force ranges 4. Securely screw the syringe to the filter. that meet this criterion are listed in Table II. NOTE: Do not touch the tip of the filter to avoid possible contamination. Any specimen that is not tested or retested within 24 hours of initial 5. Pour a minimum of 1 mL of the centrifuged cadaveric serum into the centrifugation must be recentrifuged as described in Table II. syringe. Table II: Nonfrozen PLASMA Specimens NOTE: Additional volume may be required based on the number of Centrifugation Time ABBOTT PRISM assays performed. Refer to the Specimen Volume section of this package insert. (minutes) RCF (x g) g-minutes 6. While holding the filter syringe unit over the tube, insert the plunger and 15 3,000 45,000 slowly apply pressure to deliver the filtered cadaveric serum. 20 2,250 - 3,000 45,000 - 60,000 NOTE: A clogged filter will resist pressure and no additional sample volume will pass through. 25 1,800 - 3,000 45,000 - 75,000 7. If necessary, replace the clogged filter as follows: a. Remove the sterile filter from the package. Previously frozen specimens must be mixed gently and thoroughly after b. Carefully invert the syringe to a filter-side-up position with the thawing and centrifuged such that g-minutes are between 180,000 and syringe plunger intact to prevent sample leakage. Gently remove 300,000. A refrigerated or nonrefrigerated centrifuge is acceptable for the clogged filter and dispose of it in a potentially infectious use. The acceptable time and force ranges that meet this criterion are waste container. listed in Table III. c. Securely screw the syringe to the filter. ANY previously frozen specimen that is not tested or retested within 24 d. Slowly apply pressure on the plunger to deliver the filtered cadaveric hours of initial centrifugation and not refrozen must be recentrifuged at serum into the tube. 30,000 to 75,000 g-minutes. e. Repeat this step as needed to successfully complete the Table III: Previously Frozen Specimens filtration process. NOTE: Filtered cadaveric specimens that are not tested within 24 Centrifugation Time hours of initial centrifugation must be recentrifuged, but do not need (minutes) RCF (x g) g-minutes to be refiltered. 15 12,000 180,000 Storage and Shipping 20 9,000 - 12,000 180,000 - 240,000 • Living donor specimens may be stored at 30°C or colder for up to 7 days, 2-8°C for up to 14 days or frozen at -20°C or colder for up to 6 months 25 7,200 - 12,000 180,000 - 300,000 (inclusive of shipping time). Storage at a combination of 30°C or colder and 2-8°C may not exceed 14 days. Additional Centrifugation Information • Cadaveric serum specimens may be stored at 30°C or colder for up Convert rpm to RCF as follows: RCF = 1.12 x r (rpm/1000)2 to 2 days; 2-8°C or -20°C or colder for up to 14 days (inclusive of max shipping time). Storage at a combination of these temperatures may R C F 1 0 0 0 x not exceed 14 days. Convert RCF to rpm as follows: rpm = 1. 1 2xrmax • Prior to freezing, the serum or plasma should be removed from the clot RCF - The relative centrifugal force generated during or red blood cells to avoid hemolysis. centrifugation. • Living donor specimens stored at -20°C or colder for greater than rpm - The revolutions per minute of the rotor on which the 6 months and cadaveric donor serum stored at -20°C or colder for greater specimens are being spun (usually the digital readout than 14 days may be used for informational purposes (e.g., lookback on the centrifuge will indicate the rpm). testing, discordant sample testing, clinical and validation testing). Centrifugation The time should be measured from the time the rotor • For collection of specimens from cadaveric donors, follow general Time - reaches the required RCF or rpm to the time it begins standards and/or regulations. decelerating. • When shipping specimens, package and label specimens in compliance with applicable regulations covering the transport of clinical specimens r - Radius of the rotor in millimeters. The radius measured is max and infectious substances. dependent on whether the rotor is a fixed angle rotor or a swinging bucket rotor. This value is typically provided • Twenty-six nonreactive and 78 low-level reactive living donor specimens with the rotor by the manufacturer. For the fixed angle showed no qualitative performance differences when subjected to 6 freeze/thaw cycles. However, some specimens that have undergone rotor, rmax is the measure of the distance from the rotor axis (center) to the bottom of the specimen tube in the multiple freeze/thaw cycles or have been stored frozen for prolonged rotor or rotor adapter. For the swinging bucket rotor, periods may give erroneous or inconsistent test results. rmax is the measure of the distance from the rotor axis • Twenty-five nonreactive and 24 low-level reactive cadaveric specimens (center) to the bottom of the specimen tube in the rotor that were received frozen, showed no qualitative performance adapter or bucket at full extension. differences when subjected to 1 additional freeze/thaw cycle. However, some cadaveric specimens that have undergone multiple freeze/thaw NOTE: If custom tube adapters (i.e., adapters not defined cycles or have been stored frozen for prolonged periods may give by the centrifuge manufacturer) are used, then the radius erroneous or inconsistent test results. (rmax) should be manually measured in millimeters and the RCF calculated. g-minutes - The unit of measure for the product of RCF (x g) and centrifugation time (minutes).

5 Specimen Volume • Perform the prime procedure. (Refer to the ABBOTT PRISM Operations The specimen volume required to test a single sample on the ABBOTT Manual, Section 5). PRISM System varies according to the number of assays configured, which • Initiate sample processing. Gently invert calibrators and assay controls assays are selected, and the type (size) of specimen container used. The in the calibrator pack several times. Open the bottles in the calibrator ABBOTT PRISM HIV O Plus assay requires a 100 µL sample dispense. For pack and place in the calibrator rack. Load the calibrator rack and ABBOTT PRISM Sample Cups, the minimum specimen volume required sample racks, including the run controls. (Refer to the QUALITY for one ABBOTT PRISM HIV O Plus assay is 400 µL. For either primary CONTROL PROCEDURES, Controls, Control Handling Procedure, in or aliquot tubes, or additional assay volume requirements, refer to the this package insert.) ABBOTT PRISM Operations Manual, Section 5. • After the calibrators and positive assay controls have been automatically pipetted, remove the calibrator rack. Close the calibrator and positive PROCEDURE assay control bottles and return them to 2-8°C storage. Materials Provided • Each specimen is initially tested once, unless the operator overrides • 3L68-68 ABBOTT PRISM HIV O Plus Assay Kit this automatic function of the ABBOTT PRISM System. Materials Required but not Provided • Sample racks may be removed after the samples have been pipetted. • 3L68-58 ABBOTT PRISM HIV O Plus Wash Kit NOTE: No operator interaction is required for the following steps, which are automatically carried out by the ABBOTT PRISM System: • 1A75-02 or 3L27-02 ABBOTT PRISM reaction tray transport, calibrator/assay control/sample/release control • 1A75-01 or 3L27-01 ABBOTT PRISM pipetting, incubation, reagent dispense, sample reading, data reduction, • 5A07-01 ABBOTT PRISM run validity and result determination. • After specimen processing is complete, perform the purge procedure. • 5A07-10 ABBOTT PRISM (Refer to the ABBOTT PRISM Operations Manual, Section 5). • 6A36-60 ABBOTT PRISM Accessory Kit Refer to the ABBOTT PRISM Operations Manual, Section 3, for a detailed • 3E60-10 ABBOTT PRISM Run Control Kit description of ChLIA procedures. The ABBOTT PRISM HIV O Plus assay or is a three-step ChLIA procedure. • 3E60-11 ABBOTT PRISM Positive Run Control Kit QUALITY CONTROL PROCEDURES • 6A36-31 ABBOTT PRISM Calibration • Protective Disposable Gloves The ABBOTT PRISM HIV O Plus Negative and Positive Calibrators and • Disinfectant the ABBOTT PRISM HIV O Plus HIV-2 Positive Assay Control (1) are automatically tested in triplicate at the beginning of each batch. The • Purified Water-rinsed or Clean Disposable Measuring Equipment ABBOTT PRISM HIV O Plus HIV-1 Group O Positive Assay Control (2) is For Cadaveric Specimens Only automatically tested once at the beginning of each batch. The ABBOTT • 2P41-01 Millipore GV Filters PRISM System will not generate results when calibrator or positive assay control values do not meet specifications. This may indicate either • 10 cc Sterile Syringes deterioration or contamination of reagents or instrument failure. Additional Materials Available Controls • 7B36-01 ABBOTT PRISM 1. The ABBOTT PRISM Positive Control MUST be included as the last • 1A75-10 or 3L27-10 ABBOTT PRISM sample in each batch as a release control. The operator is prompted to • 7A03-01 or 3L00-01 ABBOTT PRISM include this control as the last sample in every batch, and the ABBOTT PRISM Positive Control is automatically tested as a single replicate. • 7A03-30 or 3L00-30 ABBOTT PRISM This control must meet specifications defined in the ABBOTT PRISM • 7A03-31 ABBOTT PRISM Run Control package insert or the ABBOTT PRISM Positive Run Control package insert in order to validate the system functionality and release ABBOTT PRISM HIV O Plus Assay Procedure sample results. If this control does not meet specifications, refer to Key procedures that require operator interaction for testing samples are the ABBOTT PRISM Operations Manual, Section 10, for additional listed below. For detailed information concerning batch time, maximum information. batch size, reagent handling and loading and associated procedural steps, refer to the ABBOTT PRISM Operations Manual, Sections 2, 5, and 7. 2. Additional controls may be run at the operator’s discretion (refer to the ABBOTT PRISM Operations Manual, Section 3). • Enter a Plan Work Load (refer to the ABBOTT PRISM Operations Manual, Section 5). Invalidate controls: Additional controls may be run anywhere within a batch as an invalidate control. Specifications may be assigned to • Replace reagents as needed (refer to the ABBOTT PRISM Operations invalidating controls. If an invalidate control fails to meet assigned Manual, Sections 5 and 7). Prepare diluted probe, if necessary. Refer specifications, sample processing is shutdown and no sample results to the Preparation of the Diluted Probe section of this package insert. are calculated or provided by the instrument. When an invalidate NOTE: Gently invert each component several times prior to loading control meets assigned specifications, sample processing continues, on the ABBOTT PRISM System to ensure a homogeneous solution. and a valid release control (ABBOTT PRISM Positive Control) result Additional gentle inversion may be required to thoroughly resuspend is required to release data. microparticles. Avoid foaming. Gently invert calibrators and assay Non-validating controls: Additional controls may be run anywhere controls in the calibrator pack several times prior to each use. Each within a batch as a non-validating control. Specifications may be component of the ABBOTT PRISM HIV O Plus Wash Kit should be at assigned to non-validating controls. A valid release control (ABBOTT room temperature (15-30°C) and then mixed before loading onto the PRISM Positive Control) result is required to release data. If the user- ABBOTT PRISM System. assigned specifications for the non-validating control(s) are not met • Verify that all tubing label symbols match the symbols on each reagent and the release control specifications are met, there will be no effect label. (Refer to the symbol key in the REAGENTS section of this on sample processing. In this case, reactive sample results must not package insert and the ambient reagent bay and refrigerator diagrams be considered invalid. provided with the ABBOTT PRISM System). 3. Control Handling Procedure • Verify that all tubing is securely fastened to the corresponding wash and reagent bottles. a. Place run control adapters into the sample rack. The adapters can be placed in any rack position except 1, 2, 27, or 28. • Inspect the waste containers. Empty and clean as defined in the ABBOTT PRISM Operations Manual, Section 9, if necessary. b. Place each run control bottle into an adapter in the sample rack such that when the bottle flip-top cap is opened, it can be snapped • Prepare activator solution (refer to the Preparation of Activator into an open position within the adapter. Solution section of this package insert) and load onto the ABBOTT PRISM System. c. As mentioned above, place an ABBOTT PRISM Positive Control after the last sample tested in the batch. The controls can be • Verify that an adequate number of ABBOTT PRISM Reaction Trays placed in any rack position except 1, 2, 27, or 28. are in the Tray Loader. • Verify that an adequate number of ABBOTT PRISM Pipette Tips are Refer to the ABBOTT PRISM Operations Manual, Section 3, for additional in the Pipette Tip Racks. information on calibrators, assay controls, and run controls.

6 ASSAY PARAMETER SPECIFICATIONS System Errors The ABBOTT PRISM HIV O Plus assay parameter specifications have been For a description of the error codes that appear on ABBOTT PRISM System factory set. These parameters cannot be printed, displayed, or edited. reports, refer to the ABBOTT PRISM Operations Manual, Section 10. RESULTS LIMITATIONS OF THE PROCEDURE • This assay was designed and validated for use with individual human Calculation of Cutoff and S/CO Values serum and plasma specimens. This assay has not been validated for The ABBOTT PRISM System calculates the ABBOTT PRISM HIV O Plus use with pooled specimens. assay cutoff value using the following formula: • Do not use specimens collected in heparin. Use of heparin as an Cutoff Value = Mean Negative Calibrator (NC) Net Counts + (0.15 × anticoagulant may cause a reduction in sample net counts and in Mean Positive Calibrator [PC] Net Counts) S/CO for ABBOTT PRISM HCV; therefore, heparin is not Example: Mean NC Net Counts = 1,000 recommended for any ABBOTT PRISM assay. Mean PC Net Counts = 12,000 • For living donors and cadaveric (non-heart-beating) donors, serum 1,000 + (0.15 × 12,000) = 2,800 from heparinized patients may be incompletely coagulated resulting in Cutoff Value = 2,800 potential instrument errors such as drain time errors due to the presence The ABBOTT PRISM System calculates the ABBOTT PRISM HIV O Plus of fibrin. To prevent this phenomenon, draw specimen prior to heparin assay S/CO for each sample and control using the following formula: therapy or after heparin therapy is discontinued and activated partial thromboplastin time (aPTT) levels return within normal range. S/CO = Sample Net Counts ÷ Cutoff Value • False-reactive test results can be expected with any test kit. Example: Sample Net Counts = 7,980 False-reactive test results have been observed due to nonspecific Cutoff Value = 2,800 interactions. Refer to the SPECIFIC PERFORMANCE CHARACTERISTICS 7,980 ÷ 2,800 = 2.85 section of this package insert for assay performance characteristics. S/CO = 2.85 • Some specimens that have undergone multiple freeze/thaw cycles or Interpretation of Results have been stored frozen for prolonged periods may result in erroneous or inconsistent test results. • In the ABBOTT PRISM HIV O Plus assay, specimens with net counts less than the cutoff value are nonreactive and need not be • An increased occurrence of drain time errors may be observed for tested further. Nonreactive specimens are considered negative for cadaveric specimens. anti-HIV-1 and anti-HIV-2 by the criteria of the ABBOTT PRISM • Do not use cadaveric plasma specimens. HIV O Plus assay. • All specimens, except nonfrozen plasmapheresis specimens, must be • Specimens with net counts greater than or equal to the cutoff value centrifuged according to the Preparation For Analysis section of this are considered initially reactive by the criteria of the ABBOTT PRISM package insert prior to running the assay. HIV O Plus assay. All initial reactive specimens retested within • Inadequate centrifugation of nonfrozen plasma specimens can lead to 24 hours of initial centrifugation do not require recentrifugation. All elevated reactive rates due to platelet interference. initial reactive specimens (excluding nonfrozen plasmapheresis) stored • Performance has not been established using umbilical cord blood or greater than 24 hours after initial centrifugation must be recentrifuged body fluids such as urine, saliva, semen, amniotic fluid, cerebrospinal prior to retesting according to the Preparation for Analysis section fluid, or pleural fluid. These specimens should not be tested using the of this package insert. Initially reactive specimens must be retested in ABBOTT PRISM HIV O Plus assay. duplicate using the ABBOTT PRISM HIV O Plus Assay Kit. • Do not use heat-inactivated specimens. • If the sample net counts for both retests are less than the cutoff value, the specimen is nonreactive. Nonreactive specimens are considered • Do not use specimens with obvious microbial contamination or gross negative for anti-HIV-1 and anti-HIV-2 by the criteria of the ABBOTT lipemia. PRISM HIV O Plus assay. • Do not use specimens with obvious gross hemolysis (dark red to black). • If the sample net counts for either duplicate retest are greater than No qualitative performance differences were observed when living or equal to the cutoff value, the specimen is considered repeatedly donor specimens were spiked with 500 mg/dL of hemoglobin. reactive. Repeatedly reactive results indicate the presence of No qualitative performance differences were observed for living donor anti-HIV-1 and/or anti-HIV-2 by the criteria of the ABBOTT PRISM specimens with up to 1690 mg/dL endogenous levels of hemoglobin. HIV O Plus assay. No qualitative performance differences were observed for cadaveric donor specimens with up to 631 mg/dL of hemoglobin. • Follow appropriate FDA recommendations and regulations for specimens found to be repeatedly reactive. Customers outside the • Avoid microbial contamination of reagents or wash kit components US must follow their country’s government recommendations and by carefully following handling precautions within this package insert. regulations for specimens found to be repeatedly reactive. • The ABBOTT PRISM HIV O Plus assay does not discriminate between • Because of possible nonspecific reactions due to causes other than HIV-1 and HIV-2 antibody reactivity. HIV infection, particularly when testing low prevalence populations (e.g., • A test result that is negative does not exclude the possibility of exposure blood donors), it is appropriate to further investigate specimens found to or infection with HIV-1 and/or HIV-2. Negative results in this assay to be repeatedly reactive by the ABBOTT PRISM HIV O Plus assay in individuals with prior exposure to HIV-1 and/or HIV-2 may be due to prove that HIV antibodies are indeed present. Repeatedly reactive to antibody levels below the limit of detection of this assay or lack of specimens obtained from people at increased risk for HIV infection antibody reactivity to the HIV antigens used in this assay. are usually found to contain antibodies by supplemental tests, e.g., • The presence of HIV-1 and/or HIV-2 antibodies is not a diagnosis Western blot, IFA, or RIPA. of AIDS. Follow appropriate FDA recommendations for specimens • Although the association of infectivity of donated blood or plasma found to be repeatedly reactive. Individuals who are repeatedly and the presence of anti-HIV-1/HIV-2 is strong, it is recognized that reactive should be referred for medical evaluation, which may include presently available methods for anti-HIV-1/HIV-2 detection are not additional testing. sensitive enough to detect all potentially infectious units of blood, • A person who has antibodies to HIV-1 is presumed to be infected with plasma, or possible cases of HIV-1/HIV-2 infection. A nonreactive test the virus, except a person who has participated in an HIV vaccine study result does not exclude infection. who may have developed antibodies to the vaccine and may or may not Reading Results be infected with HIV. Clinical correlation is indicated with appropriate counseling, medical evaluation, and possibly additional testing to decide Some S/CO values may be flagged with “<” or “>” symbols. For more whether a diagnosis of HIV infection is accurate. information on sample reports, refer to the ABBOTT PRISM Operations Manual, Section 5: Operating Instructions, Reports. The ABBOTT PRISM System reports sample results in net counts and S/CO. Net Counts are used by the ABBOTT PRISM System to interpret results. The S/CO value is provided in reports to show reactivity relative to the cutoff value. In the ABBOTT PRISM HIV O Plus assay, specimens with S/CO values of less than 1.00 are reported as nonreactive. Specimens with an S/CO value of greater than or equal to 1.00 are reported as reactive.

7 SPECIFIC PERFORMANCE CHARACTERISTICS Specificity based on assumed zero prevalence of antibody to HIV-1 and/or HIV-2 in blood donors was estimated in these studies to be 99.94% Assay Reproducibility (15,589/15,599) with a 95% confidence interval of 99.88% to 99.97%. Assay reproducibility was determined by testing a 6-member panel consisting of 1 specimen nonreactive for anti-HIV-1/HIV-2 (panel member An internal study was performed to evaluate 342 serum and plasma 1), 2 diluted specimens reactive for anti-HIV-1 (panel members 2 and 3), repository specimens collected from individuals with medical conditions 2 diluted specimens reactive for anti-HIV-2 (panel members 4 and 5), and unrelated to HIV infection (Table V). Four of the 342 specimens (1.17%) 1 diluted specimen reactive for anti-HIV-1 Group O (panel member 6). were initially reactive and 3 of these specimens (0.88%) were repeatedly Panel members were prepared in recalcified human plasma. Each panel reactive. Of the 3 repeatedly reactive specimens, 2 were negative by member was tested in replicates of 4 in 5 runs over 5 days with each of supplemental testing and 1 was indeterminate. 3 reagent lots at 5 sites. The Negative, Positive, and Supplemental Positive An internal study was performed to evaluate 166 specimens collected Controls were tested once at the beginning and end of each run on each from pregnant females. Specimens were collected during each trimester subchannel. The Negative and Positive Calibrators, HIV-2 Positive Assay of pregnancy (Table V). Both the initial and repeat reactive rates for these Control (1), and HIV-1 Group O Positive Assay Control (2) were tested in specimens were 0.60% (1/166). The repeatedly reactive specimen was triplicate at the beginning of each run on each subchannel. The intra-assay negative by supplemental testing. and inter-assay standard deviation (SD) and percent coefficient of variation An internal study was performed to evaluate 77 serum specimens containing (%CV) were determined with a variance component analysis34 for a random potentially interfering substances (Table V). The initial and repeat reactive effects model35 (Table IV). rates for these specimens were both 5.19% (4/77). Three specimens were Table IV positive and 1 specimen was negative by supplemental testing. ABBOTT PRISM HIV O Plus Assay Reproducibility Table V Panel Member Number of Mean Intra-assay Inter-assayb Reactivity of the ABBOTT PRISM HIV O Plus Assay in Blood Donors, or Control Replicates S/COa SD %CV SD %CV in Specimens from Individuals with Medical Conditions Unrelated to HIV Infection, in Pregnant Females, and in Specimens Containing 1 300 0.29 0.027 9.3 0.028 9.6 Potentially Interfering Substances 2 300 3.20 0.139 4.3 0.151 4.7 Number IR (% of Total) RR (% of Total) 3 299c 7.30 0.302 4.1 0.363 5.0 Category Tested (95% CI) (95% CI) 4 298d 3.01 0.086 2.9 0.149 4.9 Volunteer Donors Serum 6,284 4 (0.06) 2 (0.03) 5 298c,e 7.00 0.208 3.0 0.337 4.8 (0.02 - 0.16) (0.00 - 0.11) 6 300 3.10 0.110 3.5 0.172 5.6 Plasma 6,181 5 (0.08) 5 (0.08) Negative 300 0.31 0.028 9.0 0.029 9.4 (0.03 - 0.19) (0.03 - 0.19) Control Plasmapheresis 3,134 3 (0.10) 3 (0.10) Positive 300 2.83 0.124 4.4 0.128 4.5 Donors (0.02 - 0.28) (0.02 - 0.28) Control Total Donors 15,599 12 (0.08) 10 (0.06) Supplemental 300 2.67 0.086 3.2 0.146 5.5 (0.04 - 0.13) (0.03 - 0.12) Positive Control Medical Conditions Unrelated to HIV HIV-1 Group O 450 5.87 0.245 4.2 0.302 5.1 Infectiona 342 4 (1.17) 3 (0.88)b Positive Assay Control (2) Pregnant Females 166 1 (0.60) 1 (0.60) Specimens Containing a Cutoff Value = Mean Negative Calibrator Net Counts + (0.15 × Mean Positive Potentially Interfering Calibrator Net Counts) Substancesc 77 4 (5.19) 4 (5.19) Calibrator Number of Mean Net Intra-assay Inter-assay IR = Initially Reactive; RR = Repeatedly Reactive; CI = Confidence Interval or Control Replicates Counts SD %CV SD %CV a Specimens from individuals with medical conditions unrelated to HIV infection Negative Calibrator 448f 731 43.3 5.9 57.9 7.9 included the following categories: anti-CMV positive (17), anti-EBV positive (18), Positive Calibrator 448f 9,800 476.4 4.9 642.7 6.6 anti-HSV positive (21), acute and recovered HAV infection (16), anti-HBs positive (20), anti-HTLV-I/HTLV-II positive (21), anti-HCV positive (27), rubella HIV-2 Positive Assay 450 10,107 354.9 3.5 504.3 5.0 antibody positive (26), toxoplasma antibody positive (20), E. coli infections (1), Control (1) yeast infection (13) syphilis serology positive (17), anti-nuclear antibody b Inter-assay variability includes intra-assay variability. positive (17), rheumatoid factor positive (17), influenza vaccine recipients (46), c One replicate was invalid due to instrument detection of high dark counts. small pox vaccine recipients (10), elevated IgG and elevated IgM (12), and d Two replicates were removed because the sample was suspected of being oncology (23). b contaminated. The 3 repeatedly reactive specimens included the following categories: anti-CMV e One replicate that had an S/CO value of 32.13 was excluded from the analysis. positive, anti-HBs positive, and anti-HTLV-I/HTLV-II positive. c When this replicate was included in the analysis, the mean S/CO was 7.09, the Specimens contained the following potentially interfering substances: elevated intra-assay SD was 1.434, the intra-assay %CV was 20.2, the inter-assay SD was triglycerides (28), elevated bilirubin (26), and elevated hemoglobin (23). 1.480, and the inter-assay %CV was 20.9. f Assay Sensitivity Two replicates were invalid due to instrument detection of high dark counts. A total of 1,388 serum and plasma specimens from individuals known to Assay Specificity be positive for HIV antibodies were tested with the ABBOTT PRISM HIV O A total of 6,284 fresh serum specimens and 6,181 fresh plasma specimens Plus assay (Table VI). Of the 1,388 specimens tested, 1,388 specimens from volunteer blood donors were collected and tested at 4 geographically (100.00%) were repeatedly reactive. distinct blood centers (Table V). A total of 3,134 specimens from Plasma specimens from individuals at increased risk for HIV infection plasmapheresis donors were collected and tested at a fifth geographically were tested with the ABBOTT PRISM HIV O Plus assay (Table VI). This distinct blood center (Table V). The initial and repeat reactive rates for the study included a total of 605 specimens from the United States and 512 serum specimens were 0.06% (4/6,284) and 0.03% (2/6,284), respectively. specimens from an HIV-2 endemic area (Republic of Côte d’Ivoire). Of the Both the initial and repeat reactive rates for the plasma specimens 1,117 specimens tested, 156 specimens (13.97%) were repeatedly reactive. were 0.08% (5/6,181). Both the initial and repeat reactive rates for the Of the 156 repeatedly reactive specimens, 136 specimens (87.18%) tested plasmapheresis donor specimens were 0.10% (3/3,134). Repeatedly reactive positive by supplemental testing. specimens were further tested using an FDA-licensed HIV-1 Western blot, The overall sensitivity was estimated in these studies to be an FDA-licensed HIV-2 EIA, and a research use only HIV-2 Western blot. 100.00% (1,524/1,524) with a 95% confidence interval of 99.76% to Based on these supplemental test results, 8 of the 10 specimens were 100.00%. negative and 2 specimens were indeterminate.

8 Table VI Table VIII Reactivity of the ABBOTT PRISM HIV O Plus Assay Performance of the ABBOTT PRISM HIV O Plus Assay in Individuals Known to be Positive for HIV Antibodies, on Seroconverting Donors Compared and at Increased Risk for HIV Infection to an FDA-licensed HIV-1/HIV-2 Assay ABBOTT PRISM ABBOTT PRISM FDA-licensed HIV O Plus Number Positive by Number HIV O Plus HIV-1/HIV-2 Assay Number Number RR Supplemental Testing Panel Tested Number RR Number RR Category Tested (% of Total) (% of RR) 9077 28 14 14 Preselected 1,007 1,007 (100.00) 1,007 (100.00) BCP6243 10 3 3 Anti-HIV-1 Positivea Preselected 328 328 (100.00) 328 (100.00) PRB910 7 5 5 Anti-HIV-2 Positive PRB916 6 2 2 Anti-HIV-1 53 53 (100.00) 53 (100.00) PRB923 13 5a 4 b Group O Positive PRB924 8 3 3 Increased Risk for PRB925 6 2 2 HIV Infection United Statesc 605 71 (11.74) 55 (77.46) PRB926 6 2 2 HIV-2 Endemic 512 85 (16.60) 81 (95.29) PRB928 5 4 4 Aread PRB931 9 4 4 e Total 2,505 1,544 (61.64) 1,524 (98.70) PRB932 8 5 5 RR = Repeatedly Reactive PRB940 8 6 6 a The preselected anti-HIV-1 positive category included 809 specimens from asymptomatic individuals, 99 specimens from symptomatic individuals, and 99 PRB941 6 3 3 specimens from individuals diagnosed with AIDS. PRB944 6 2 2 b Thirty-one specimens were diluted 1:10, 18 specimens were diluted 1:20, and PRB947 4 3 3 4 specimens were undiluted. PRB951 6 1 1 c The following risk factors were included: sex with HIV infected partner, men who have sex with men, intravenous drug users, multiple sex partners, and patients PRB955 5 2 2 with sexually transmitted diseases. PRB959 7 5 5 d The following risk factors were included: sex with an HIV infected partner, men SV0321 5 3 3 who have sex with men, intravenous drug users, and multiple sex partners. e Of these 2,505 specimens, an additional 5 specimens were determined to be SV0401 7 4 4 repeatedly reactive by a licensed reference test and negative by the ABBOTT Total 160 78 77 PRISM HIV O Plus Assay. Of the additional 5 specimens, none were positive by RR = Repeatedly Reactive supplemental testing. a One of the 5 reactive specimens was negative with an FDA-licensed HIV-1/HIV-2 An internal study was performed to test specimens from individuals known assay and a Western blot. It was positive with both an HIV-1 antigen and a PCR to be positive for HIV-1 Group M antibodies. The Group M subtypes included assay. in this study are shown in Table VII. A total of 276 plasma specimens were tested with the ABBOTT PRISM HIV O Plus assay. Of these 276 specimens PERFORMANCE CHARACTERISTICS OF tested, 276 specimens (100.00%) were reactive. CADAVERIC SERUM TESTING Table VII Reproducibility HIV-1 Group M Subtypes Tested Twenty-four postmortem serum specimens, collected up to 18.2 hours ABBOTT PRISM HIV O Plus after death, and 30 living donor serum specimens were spiked with human Subtype Number Tested plasma reactive for anti-HIV-1 or anti-HIV-2 to create low-level reactive A 23 specimens. Each specimen was tested once per day over 6 different days with each of 3 ABBOTT PRISM HIV O Plus reagent lots. Inter-assay and B 14 total %CV values were determined (Table IX). C 14 Table IX D 20 ABBOTT PRISM HIV O Plus Assay Reproducibility F 4 Between- G 16 Specimen Number of Mean Specimen Totala Category Replicates S/CO SD %CV SD %CV CRF01a 61 CRF02 22 Postmortem 432 4.64 0.506 10.9 0.717 15.4 CRF09 1 Living Donor 540 4.11 0.454 11.0 0.688 16.8 a CRF11 11 Total variability includes within-specimen, between-specimen, between-lot, and specimen-lot interaction variance components. CRF13 3 URFb 87 Specificity Assay specificity was determined by testing postmortem serum specimens, Total 276 collected up to 18.8 hours after death, and living donor serum specimens. a CRF = circulating recombinant form Each specimen was tested once. Three ABBOTT PRISM HIV O Plus b URF = unique recombinant form reagent lots were used (Table X). Sensitivity was also evaluated using 160 serial bleeds from 20 commercially Table X available seroconversion panels. Each specimen was tested with the ABBOTT PRISM HIV O Plus Assay Reactivity ABBOTT PRISM HIV O Plus assay, which detected the presence of HIV Specimen Number of Median Nonreactive Initial Reactive antibody at the same time or earlier than an FDA-licensed HIV-1/HIV-2 Category Specimens S/CO (% of Total) (% of Total) assay (Table VIII). Postmortem 56 0.35 56 (100.00) 0 (0.00) Living Donor 60 0.25 60 (100.00) 0 (0.00) The ABBOTT PRISM HIV O Plus assay has an estimated specificity of 100.00% (56/56) (95% binomial confidence interval of 93.62% - 100.00%) for postmortem serum specimens.

9 Sensitivity 20. Gürtler LG, Hauser PH, Eberle J, et al. A new subtype of human Postmortem specimens, collected up to 20.5 hours after death, and immunodeficiency virus type 1 (MVP-5180) from Cameroon. J Virol living donor specimens were spiked with human plasma reactive for 1994;68(3):1581-5. anti-HIV-1 or anti-HIV-2 to create low-level reactive specimens.a Each 21. De Leys R, Vanderborght B, Vanden Haesevelde M, et al. Isolation specimen was tested once on each of 3 ABBOTT PRISM HIV O Plus and partial characterization of an unusual human immunodeficiency reagent lots (Table XI). retrovirus from two persons of West-Central African origin. J Virol Table XI 1990;64(3):1207-16. ABBOTT PRISM HIV O Plus Assay Reactivity 22. Yamaguchi J, Vallari AS, Swanson P, et al. Evaluation of HIV type 1 group O isolates: identification of five phylogenetic clusters. AIDS Specimen Number of Mean Nonreactive Initial Reactive Res Hum Retroviruses 2002;18(4):269-82. Category Specimens S/CO (% of Total) (% of Total) 23. Simon F, Mauclère P, Roques P, et al. Identification of a new human Postmortem 59 4.08 0 (0.00) 59 (100.00) immunodeficiency virus type 1 distinct from group M and group O. Living Donor 60 3.10 0 (0.00) 60 (100.00) Nat Med 1998;4(9):1032-7. The ABBOTT PRISM HIV O Plus assay has an estimated sensitivity of 24. Ayouba A, Souquières S, Njinku B, et al. HIV-1 group N among HIV-1- 100.00% (95% binomial confidence interval of 93.94% - 100.00%) for seropositive individuals in Cameroon. AIDS 2000;14(16):2623-5. postmortem serum specimens. 25. Yamaguchi J, McArthur CP, Vallari A, et al. HIV-1 group N: evidence a Spiked reactive samples were initially tested within 24 hours of spiking. of ongoing transmission in Cameroon. AIDS Res Hum Retroviruses 2006;22(5):453-7. BIBLIOGRAPHY 26. US Department of Labor, Occupational Safety and Health 1. Barré-Sinoussi F, Chermann JC, Rey F, et al. 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Laboratory Workers From Occupationally Acquired Infections; Approved Guideline—Fourth Edition. CLSI Document M29-A4. Wayne, PA: CLSI; 4. Piot P, Plummer FA, Mhalu FS, et al. AIDS: an international 2014. perspective. Science 1988;239:573-9. 30. CDC. Guidelines for the prevention of transmission of human 5. Clavel F, Guétard D, Brun-Vézinet F, et al. Isolation of a new human immunodeficiency virus and hepatitis B virus to health-care and retrovirus from West African patients with AIDS. Science 1986;233: public-safety workers. MMWR 1989;38(S-6):16. 343-6. 31. Sehulster LM, Hollinger FB, Dreesman GR, et al. Immunological 6. Clavel F. HIV-2, the West African AIDS virus. AIDS 1987;1(3):135 40. and biophysical alteration of hepatitis B virus antigens by sodium 7. Couroucé A-M and the “Retrovirus” study group of the French Society hypochlorite disinfection. Appl Envir Microbiol 1981;42(5):762-7. of Blood Transfusion. A prospective study of HIV-2 prevalence in 32. Clinical and Laboratory Standards Institute. Clinical Laboratory Waste France. AIDS 1988;2(4):261-5. Management: Approved Guideline-Second Edition. CLSI Document 8. Schim van der Loeff MF, Aaby P. Towards a better understanding of GP5-A2. Wayne, PA: Clinical and Laboratory Standards Institute, the epidemiology of HIV-2. AIDS 1999;13(suppl A):S69-S84. 2002;22(3):1-23, 32-44. 9. Robertson DL, Anderson JP, Bradac JA, et al. HIV-1 nomenclature 33. US Environmental Protection Agency. EPA Guide for Infectious Waste proposal. In: Kuiken C, Foley B, Hahn B, et al, eds. Human Retroviruses Management. Publication No. EPA/530-SW-86-014. Washington, DC: and AIDS 1999. Los Alamos, NM: Theoretical Biology and Biophysics US Environmental Protection Agency; 1986:1-1–5-5, R1–R3, A1–A24. Group at Los Alamos National Laboratory; 1999:492-505. 34. Box GEP, Hunter WG, Hunter JS. Statistics for Experimenters: An 10. Frequently asked questions: HIV sequence database. Subtypes and Introduction to Design, Data Analysis, and Model Building. New York, recombinants section. Available at: http://www.hiv.lanl.gov/content/ NY: John Wiley & Sons, Inc; 1978:510-39, 571-83. sequence/HIV/FAQ.html. Accessed May 22, 2008. 35. SAS Institute Inc. The MIXED Procedure. In: SAS Technical Report 11. Peeters M, Sharp PM. Genetic diversity of HIV-1: the moving target. P-229, SAS/STAT Software: Changes and Enhancements, Release AIDS 2000;14(suppl 3):S129-S140. 6.07. Cary, NC: SAS Institute Inc; 1992:289-366. 12. McCutchan FE. Understanding the genetic diversity of HIV-1. AIDS 2000;14(suppl 3):S31-S44. ABBOTT PRISM is a trademark of Abbott Laboratories in various jurisdictions. 13. Peeters M. Recombinant HIV sequences: their role in the global All other trademarks are property of their respective owners. epidemic. In: Kuiken C, Foley B, Hahn B, et al, eds. HIV Sequence Compendium 2000. Los Alamos, NM: Theoretical Biology and Biophysics Group at Los Alamos National Laboratory; 2000:54-72. Abbott GmbH & Co. KG 14. Hampl H, Sawitzky D, Stöffler-Meilicke M, et al. First case of HIV-1 Max-Planck-Ring 2 subtype O infection in Germany. Infection 1995;23(6):369-70. 65205 Wiesbaden Germany 15. Loussert-Ajaka I, Chaix M-L, Korber B, et al. Variability of human +49-6122-580 immunodeficiency virus type 1 group O strains isolated from Cameroonian patients living in France. J Virol 1995;69(9):5640-9. March 2019 16. Soriano V, Gutiérrez M, García-Lerma G, et al. First case of HIV-1 ©2009, 2019 Abbott Laboratories group O infection in Spain. Vox Sang 1996;71:66. 17. Rayfield MA, Sullivan P, Bandea CI, et al. HIV-1 group O virus identified for the first time in the United States. Emerg Infect Dis 1996;2(3):209-12. 18. Peeters M, Gueye A, Mboup S, et al. Geographical distribution of HIV-1 group O viruses in Africa. AIDS 1997;11(4):493-8. 19. Sullivan PS, Do AN, Robbins K, et al. Surveillance for variant strains of HIV: subtype G and group O HIV-1. JAMA 1997;278(4):292.

10 en ABBOTT PRISM Run Control Kit 3E60-10 G1-0321/R10 ABBOTT PRISM Run Control Kit Revised June 2014

Customer Service: Contact your local representative or find country specific contact information on www.abbottdiagnostics.com

Package insert instructions must be carefully followed. Reliability of assay results cannot be guaranteed if there are any deviations from the instructions in this package insert.

Key to Symbols

Lot Number Manufacturer

List Number Positive Control In Vitro Diagnostic Medical Device Negative Control

Consult instructions for use Contains Sodium Azide. Contact with acids liberates very toxic gas. Caution Product of USA Store at 2-8°C

Run Control Adapters Expiration Date

See REAGENTS section for a full explanation of symbols used in reagent component naming.

3E60-01-10_Eng_ReIn.indd 1 6/9/2014 8:46:29 AM COLOR: PMS 525 Black LE: Mark DTP: Ania NAME ANd INTENdEd USE • The human plasma used in the supplemental positive control is reactive The ABBOTT PRISM Run Control Kit contains multi-constituent positive for anti-HIV-2 and anti-HTLV-II. Plasma is nonreactive for HBsAg, HIV-1 controls and a negative control for use as quality controls with the ABBOTT RNA or HIV-1 Ag, and anti-HCV. Supplemental Positive Control may be PRISM Assay Kits. The ABBOTT PRISM Positive Control is required as a cross-reactive with HTLV-I antigens. release control and must be tested as the last sample in each batch to • The human plasma used in the negative control is nonreactive validate system function and release sample results. The ABBOTT PRISM for anti-HBc, anti-HBs, anti-HTLV-I/HTLV-II, HBsAg, HIV-1 RNA or Supplemental Positive and Negative Controls can be used at any point in HIV-1 Ag, anti-HIV-1/HIV-2, and anti-HCV. a batch as a quality control. • This product contains sodium azide; for a specific listing, refer to the REAGENTS section of this package insert. Contact with acids liberates SUMMARy ANd ExPlANATION very toxic gas. This material and its container must be disposed of in Of ThE TEST a safe way. Refer to the ABBOTT PRISM assay package inserts. • Safety Data Sheets are available at www.abbottdiagnostics.com or contact your local representative. REAGENTS Kit contains: handling Precautions • Do not use controls beyond the expiration date. • 2 Bottles (10 mL each) Positive Control (Human). • Do not mix controls from different bottles. Purified anti-HBc IgG (Concentration: 0.9 - 2.6 PEI* Units/mL) and recalcified inactivated plasma reactive for HBsAg (Concentration: • Do not freeze controls. 0.10 - 0.40 ng/mL), anti-HCV (Minimum activity: 1.02 sample to cutoff • Failure to adhere to instructions in the ABBOTT PRISM Operations [S/CO]), anti-HIV-1 (Minimum activity: 1.02 S/CO) and anti-HTLV-I Manual or package insert may result in erroneous test results. (Minimum activity: 1.02 S/CO). Plasma is also tested for HIV-1 either • Use caution when handling samples, control bottles, and control caps by an HIV-1 antigen test and is nonreactive, or by an HIV-1 NAT, and to prevent cross contamination. may be reactive. Positive Control may be cross-reactive with HTLV-II antigens. Preservative: 0.1% sodium azide. (Symbol: POS) Storage Instructions • 1 Bottle (10 mL) Supplemental Positive Control (Human). • The ABBOTT PRISM Positive, Supplemental Positive, and Recalcified inactivated plasma reactive for anti-HIV-2 (Minimum Negative Controls must be stored at 2-8°C. activity: 1.02 S/CO) and anti-HTLV-II (Minimum activity: 1.02 S/CO). • When stored and handled as directed, controls are stable Supplemental Positive Control may be cross-reactive with HTLV-I until the expiration date. antigens. Preservative: 0.1% sodium azide. (Symbol: SUP) • 2 Bottles (10 mL each) Negative Control (Human). Indications of Instability or deterioration of Reagents Recalcified plasma. Preservative: 0.1% sodium azide. (Symbol: NEG) The presence of precipitates or particulate matter may indicate instability or deterioration of reagents, and those reagents should not be used. *Concentration standardized against the reference standard of the Paul Ehrlich Institute (PEI), Langen, Germany. SPECIMEN COllECTION ANd PREPARATION WARNINGS ANd PRECAUTIONS fOR ANAlySIS • Not applicable. Refer to the ABBOTT PRISM ASSAy PROCEdURE and • for In Vitro diagnostic Use. QUAlITy CONTROl PROCEdURES sections of the ABBOTT PRISM assay package inserts for details. • This kit is a quality control for ABBOTT PRISM Assay Kits. • Package insert instructions must be carefully followed. Reliability of PROCEdURE assay results cannot be guaranteed if there are any deviations from the instructions in this package insert. Materials Provided • 3E60-10 ABBOTT PRISM Run Control Kit Safety Precautions Materials Required but not Provided • 6A36-31 ABBOTT PRISM • CAUTION: This product contains human-sourced and/or potentially infectious components. Refer to the REAGENTS section for use with of this package insert. No known test method can offer complete • 6E66-68 ABBOTT PRISM HBcore Assay Kit assurance that products derived from human sources or inactivated • 6D19-68 ABBOTT PRISM HBsAg Assay Kit microorganisms will not transmit infection. Therefore, all human- sourced materials should be considered potentially infectious. It is • 3L68-68 ABBOTT PRISM HIV O Plus Assay Kit recommended that these reagents and human specimens be handled • 6D18-68 ABBOTT PRISM HCV Assay Kit in accordance with the OShA Standard on Bloodborne Pathogens.1 • 6E50-68 ABBOTT PRISM HTLV-I/HTLV-II Assay Kit Biosafety level 22 or other appropriate biosafety practices3,4 should be used for materials that contain or are suspected of containing • 6E51-68 ABBOTT PRISM HBsAg Confirmatory Kit infectious agents. These precautions include, but are not limited Refer to the ABBOTT PRISM ASSAy PROCEdURE and QUAlITy to, the following: CONTROl PROCEdURES sections of the ABBOTT PRISM assay package • Wear gloves when handling specimens or reagents. inserts for details. • Do not pipette by mouth. Instructions for Use • Do not eat, drink, smoke, apply cosmetics, or handle contact 1. Before use, thoroughly mix the contents of the run control bottle by lenses in areas where specimens or reagents are handled. gently inverting several times. Avoid foaming. It is not necessary to bring • Clean and disinfect all spills of specimens or reagents using the material to room temperature prior to placing on the instrument. an appropriate disinfectant such as 0.1% sodium hypochlorite, 2. Refer to the ABBOTT PRISM ASSAy PROCEdURE and QUAlITy or other suitable disinfectant.5,6 CONTROl PROCEdURES sections of the ABBOTT PRISM assay • Decontaminate and dispose of all specimens, reagents, and package inserts for details. other potentially contaminated materials in accordance with local, state, and federal regulations.7,8 • The human plasma used in the positive control is reactive for HBsAg, anti-HCV, anti-HIV-1, and anti-HTLV-I. Plasma is also tested for HIV-1 either by an HIV-1 antigen test and is nonreactive, or by an HIV-1 NAT, and may be reactive. Positive Control may be cross-reactive with HTLV-II antigens.

3E60-01-10_Eng_ReIn.indd 2 6/9/2014 8:46:30 AM INTERPRETATION Of RESUlTS Control results are interpreted in the same manner as sample results. The following table details the acceptable Sample to Cutoff ratio (S/CO) specifications for the ABBOTT PRISM Positive, Negative, and Supplemental Positive Controls for each assay. Refer to the Interpretation of Results section of the ABBOTT PRISM assay package inserts for details. ABBOTT PRISM Run Control Specifications S/CO Ranges

hIV O hTlV-I/ hBsAg hBcore hCV Plus hTlV-II Positive Control 1.02 to 6.00 0.20 to 0.98 1.02 to 6.00 1.02 to 6.00 1.02 to 6.00 Negative Control 0.02 to 0.98 1.02 to 4.00 0.02 to 0.98 0.02 to 0.98 0.02 to 0.98 Supplemental Positive Not Not Not Control applicable applicable applicable 1.02 to 6.00 1.02 to 6.00 lIMITATIONS Of ThE PROCEdURE Refer to the ABBOTT PRISM assay package inserts. ExPECTEd VAlUES The ABBOTT PRISM Positive Control is designed to yield a reactive result and the ABBOTT PRISM Negative Control a nonreactive result with each ABBOTT PRISM chemiluminescent immunoassay (ChLIA). The ABBOTT PRISM Supplemental Positive Control is designed to yield a reactive result with the ABBOTT PRISM HIV O Plus and HTLV-I/HTLV-II assays. BIBlIOGRAPhy 1. US Department of Labor, Occupational Safety and Health Administration, 29 CFR Part 1910.1030, Bloodborne pathogens. 2. US Department of Health and Human Services. Biosafety in Microbiological and Biomedical Laboratories. 5th ed. Washington, DC: US Government Printing Office; December 2009. 3. World Health Organization. Laboratory Biosafety Manual. 3rd ed. Geneva: World Health Organization; 2004. 4. Clinical and Laboratory Standards Institute. Protection of Laboratory Workers from Occupationally Acquired Infections: Approved Guideline— Third Edition. CLSI Document M29-A3. Wayne, PA: Clinical and Laboratory Standards Institute, 2005. 5. CDC. Guidelines for the prevention of transmission of human immunodeficiency virus and hepatitis B virus to health-care and public-safety workers. MMWR 1989;38(S-6):16S. 6. Sehulster LM, Hollinger FB, Dreesman GR, et al. Immunological and biophysical alteration of hepatitis B virus antigens by sodium hypochlorite disinfection. Appl Envir Microbiol 1981;42:762–767. 7. Clinical and Laboratory Standards Institute. Clinical Laboratory Waste Management: Approved Guideline—Second Edition. CLSI Document GP5-A2. Wayne, PA: Clinical and Laboratory Standards Institute, 2002;22(3):1–23, 32–44. 8. US Environmental Protection Agency. EPA Guide for Infectious Waste Management. Publication No. EPA/530-SW-86-014. Washington, DC: US Environmental Protection Agency, 1986:1-1–5-5, R1–R3, A1–A24.

ABBOTT PRISM is a trademark of Abbott Laboratories.

3E60-01-10_Eng_ReIn.indd 3 6/9/2014 8:46:30 AM en ABBOTT PRISM Positive Run Control Kit 3E60-11 G1-0322/R10 ABBOTT PRISM Revised June 2014 Positive Run Control Kit

Customer Service: Contact your local representative or find country specific contact information on www.abbottdiagnostics.com

Package insert instructions must be carefully followed. Reliability of assay results cannot be guaranteed if there are any deviations from the instructions in this package insert.

Key to Symbols

Lot Number Expiration Date

List Number Manufacturer

In Vitro Diagnostic Positive Control Medical Device Contains Sodium Azide. Consult instructions for use Contact with acids liberates very toxic gas.

Caution Product of USA

Store at 2-8°C Run Control Adapters

See REAGENTS section for a full explanation of symbols used in reagent component naming.

3E60-01-11_Eng_ReIn.indd 1 COLOR: PMS 560 6/9/2014 8:43:54 AM Black LE: Mark DTP: Ania NAmE ANd INTENdEd USE handling precautions The ABBOTT PRISM Positive Run Control Kit contains a multi-constituent • Do not use controls beyond the expiration date. positive control for use as quality control with the ABBOTT PRISM Assay • Do not mix controls from different bottles. Kits. The ABBOTT PRISM Positive Control is required as a release control • Do not freeze controls. and must be tested as the last sample in each batch to validate system function and release sample results. • Failure to adhere to instructions in the ABBOTT PRISM Operations Manual or package insert may result in erroneous test results. SUmmARy ANd ExplANATIoN • Use caution when handling samples, control bottles, and control caps of ThE TEST to prevent cross contamination. Refer to the ABBOTT PRISM assay package inserts. Storage Instructions REAGENTS • The ABBOTT PRISM Positive Control must be stored at 2-8°C. Kit contains: • When stored and handled as directed, controls are stable • 6 Bottles (10 mL each) Positive Control (Human). until the expiration date. Purified anti-HBc IgG (Concentration: 0.9 - 2.6 PEI* Units/mL) and recalcified inactivated plasma reactive for HBsAg (Concentration: Indications of Instability or deterioration of Reagents 0.10 - 0.40 ng/mL), anti-HCV (Minimum activity: 1.02 sample to cutoff The presence of precipitates or particulate matter may indicate instability [S/CO]), anti-HIV-1 (Minimum activity: 1.02 S/CO) and anti-HTLV-I or deterioration of reagents, and those reagents should not be used. (Minimum activity: 1.02 S/CO). Plasma is also tested for HIV-1 either by an HIV-1 antigen test and is nonreactive, or by an HIV-1 NAT, and SpECImEN CollECTIoN ANd pREpARATIoN may be reactive. Positive Control may be cross-reactive with HTLV-II antigens. Preservative: 0.1% sodium azide. (Symbol: POS) foR ANAlySIS Not applicable. Refer to the ABBoTT pRISm ASSAy pRoCEdURE and *Concentration standardized against the reference standard of the Paul QUAlITy CoNTRol pRoCEdURES sections of the ABBOTT PRISM assay Ehrlich Institute (PEI), Langen, Germany. package inserts for details. WARNINGS ANd pRECAUTIoNS • pRoCEdURE • for In Vitro diagnostic Use. materials provided • 3E60-11 ABBOTT PRISM Positive Run Control Kit • This kit is a quality control for ABBOTT PRISM Assay Kits. • Package insert instructions must be carefully followed. Reliability of materials Required but not provided assay results cannot be guaranteed if there are any deviations from • 6A36-31 ABBOTT PRISM the instructions in this package insert. for use with Safety precautions • 6E66-68 ABBOTT PRISM HBcore Assay Kit • 6D19-68 ABBOTT PRISM HBsAg Assay Kit • CAUTIoN: This product contains human-sourced and/or • 3L68-68 ABBOTT PRISM HIV O Plus Assay Kit potentially infectious components. Refer to the REAGENTS section • 6D18-68 ABBOTT PRISM HCV Assay Kit of this package insert. No known test method can offer complete • 6E50-68 ABBOTT PRISM HTLV-I/HTLV-II Assay Kit assurance that products derived from human sources or inactivated microorganisms will not transmit infection. Therefore, all human- Refer to the ABBoTT pRISm ASSAy pRoCEdURE and QUAlITy sourced materials should be considered potentially infectious. It is CoNTRol pRoCEdURES sections of the ABBOTT PRISM assay package recommended that these reagents and human specimens be handled inserts for details. in accordance with the oShA Standard on Bloodborne pathogens.1 Biosafety level 22 or other appropriate biosafety practices3,4 should Instructions for Use be used for materials that contain or are suspected of containing 1. Before use, thoroughly mix the contents of the run control bottle by infectious agents. These precautions include, but are not limited gently inverting several times. Avoid foaming. It is not necessary to bring to, the following: the material to room temperature prior to placing on the instrument. • Wear gloves when handling specimens or reagents. 2. Refer to the ABBoTT pRISm ASSAy pRoCEdURE and QUAlITy CoNTRol pRoCEdURES sections of the ABBOTT PRISM assay • Do not pipette by mouth. package inserts for details. • Do not eat, drink, smoke, apply cosmetics, or handle contact lenses in areas where specimens or reagents are handled. INTERpRETATIoN of RESUlTS • Clean and disinfect all spills of specimens or reagents using an Control results are interpreted in the same manner as sample results. appropriate disinfectant such as 0.1% sodium hypochlorite, or The following table details the acceptable Sample to Cutoff ratio (S/CO) other suitable disinfectant.5,6 specifications for the ABBOTT PRISM Positive Control for each assay. Refer to the Interpretation of Results section of the ABBOTT PRISM assay • Decontaminate and dispose of all specimens, reagents, and package inserts for details. other potentially contaminated materials in accordance with local, state, and federal regulations.7,8 ABBoTT pRISm positive Run Control Specifications S/Co Ranges • The human plasma used in the positive control is reactive for HBsAg, anti-HCV, anti-HIV-1, and anti-HTLV-I. Plasma is also tested for hIV o hTlV-I/ HIV-1 either by an HIV-1 antigen test and is nonreactive, or by an hBsAg hBcore hCV plus hTlV-II HIV-1 NAT, and may be reactive. Positive Control may be cross-reactive Positive with HTLV-II antigens. Control 1.02 to 6.00 0.20 to 0.98 1.02 to 6.00 1.02 to 6.00 1.02 to 6.00 • This product contains sodium azide; for a specific listing, refer to the REAGENTS section of this package insert. Contact with acids liberates lImITATIoNS of ThE pRoCEdURE very toxic gas. This material and its container must be disposed of in Refer to the ABBOTT PRISM assay package inserts. a safe way. • Safety Data Sheets are available at www.abbottdiagnostics.com or ExpECTEd VAlUES contact your local representative. The ABBOTT PRISM Positive Control is designed to yield a reactive result with each ABBOTT PRISM chemiluminescent immunoassay (ChLIA).

3E60-01-11_Eng_ReIn.indd 2 6/9/2014 8:43:54 AM BIBlIoGRAphy 1. US Department of Labor, Occupational Safety and Health Administration, 29 CFR Part 1910.1030, Bloodborne pathogens. 2. US Department of Health and Human Services. Biosafety in Microbiological and Biomedical Laboratories. 5th ed. Washington, DC: US Government Printing Office; December 2009. 3. World Health Organization. Laboratory Biosafety Manual. 3rd ed. Geneva: World Health Organization; 2004. 4. Clinical and Laboratory Standards Institute. Protection of Laboratory Workers from Occupationally Acquired Infections: Approved Guideline— Third Edition. CLSI Document M29-A3. Wayne, PA: Clinical and Laboratory Standards Institute, 2005. 5. CDC. Guidelines for the prevention of transmission of human immunodeficiency virus and hepatitis B virus to health-care and public- safety workers. MMWR 1989;38(S-6):16S. 6. Sehulster LM, Hollinger FB, Dreesman GR, et al. Immunological and biophysical alteration of hepatitis B virus antigens by sodium hypochlorite disinfection. Appl Envir Microbiol 1981;42:762-767. 7. Clinical and Laboratory Standards Institute. Clinical Laboratory Waste Management: Approved Guideline—Second Edition. CLSI Document GP5-A2. Wayne, PA: Clinical and Laboratory Standards Institute, 2002;22(3):1-23, 32-44. 8. US Environmental Protection Agency. EPA Guide for Infectious Waste Management. Publication No. EPA/530-SW-86-014. Washington, DC: US Environmental Protection Agency; 1986:1-1-5-5, R1-R3, A1-A24.

ABBOTT PRISM is a trademark of Abbott Laboratories.

3E60-01-11_Eng_ReIn.indd 3 6/9/2014 8:43:55 AM